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CDMOs: The Modern Backbone of Biopharmaceutical Development

Contract development and manufacturing organizations can help streamline drug development

by
Leonardo Magneschi, PhD

Leonardo Magneschi, PhD, has over 12 years of experience in molecular biology and the engineering of plants and microorganisms. He completed his PhD in plant and microbial biotechnology in 2011,...

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The biopharmaceutical industry has experienced rapid growth over the last few years. This expansion generates both opportunities and challenges: a diverse range of potential therapeutic targets has been identified, but there is pressure to accelerate new biotherapeutic drugs to market. Many companies lack the time, space, resources, and expertise to develop new cell lines or manufacturing technologies in-house. This is where a contract development and manufacturing organization (CDMO) can help, stepping in to offer the specialized support, knowledge, and infrastructure needed to expedite the drug development process.

The complex landscape of biopharmaceutical development

Biopharmaceuticals are some of the most significant accomplishments of modern science. Unlike conventional synthetic drugs, bio-based treatments are produced in living cells, resulting in a molecularly and physiologically complex therapeutic product that offers high specificity and efficacy, and minimizes side effects .1,2 These benefits have led to significant growth in the biopharmaceutical industry, which makes up 20 percent of the pharmaceutical market today, with room for future expansion.1 In fact, the rate of growth in the biopharmaceutical sector currently sits at over eight percent, double that of conventional drug manufacturing.1,3

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However, developing an effective biopharmaceutical product presents operational and technological challenges. Firstly, a suitable biological host—normally bacteria, yeast, or mammalian cells2—must be selected and genetically modified to produce a protein or other molecule of interest. The cell line capable of producing the desired product then needs to be cultured in the carefully controlled environment of a reactor vessel under conditions that allow it to thrive.1 Following successful target protein production, the resulting therapeutic molecules must then be separated from the cells and media in which they were produced, and the formulation fine-tuned before entering the pre-clinical and clinical trial stages of drug development. Manufacturing large molecules for therapeutic use at an industrial scale requires significant bioengineering expertise, in addition to cutting-edge manufacturing capabilities and infrastructure.

Working with a CDMO can not only increase the speed, reliability, and reproducibility of drug development protocols, but it can also reduce risk.

The advantages of partnering with a CDMO

Fortunately, CDMOs can offer abundant resources, from state-of-the-art facilities to teams of specialist scientists, without the need for significant upfront investment by pharmaceutical organizations. As a result, around 44 percent of life sciences companies currently outsource most or all of their drug development processes.4 Entering into a partnership with a reliable and reputable CDMO can be a major asset to biopharmaceutical companies tackling a complex drug development pipeline, saving them time and money while minimizing risks and optimizing outcomes.

Accelerating drug development

Outsourcing all of the infrastructure, technology, and expertise required to manufacture a biological treatment can effectively address the challenges of the drug development pathway. An effective CDMO will have the capabilities to support companies through every step of this pipeline, from host selection to manufacturing and analytical testing. A long-term CDMO partnership can lead to streamlined development and manufacturing.

Minimizing risk

Working with a CDMO can not only increase the speed, reliability, and reproducibility of drug development protocols, but it can also reduce risk. Bringing a new therapeutic product to market comes with huge risks for pharmaceutical companies; it requires a sizable financial commitment to implement all of the required processes in-house, without any guarantee of achieving a successful clinical outcome. Outsourcing this infrastructure to a CDMO, which will already have a wide array of specialized equipment in its toolkit—as well as a dedicated manufacturing space and experienced laboratory staff—can significantly reduce this risk.

Regulatory support

Once a company has produced a clinically effective drug, it still needs to adhere to strict regulations before it can reach pharmacy shelves. Staying up to date with constantly evolving regulations can be challenging, but a comprehensive CDMO offering will include regulatory support to help biopharmaceutical companies navigate the complex and time-consuming submissions process. Partnering with a CDMO therefore provides a significant competitive advantage, accelerating regulatory approval to ensure that products are first to market.

Opportunities for scale-up

Some biopharmaceutical companies may be able to apply a bioengineering process on a small scale in a laboratory, but bringing a new drug to market typically requires developing processes that can be scaled to large volumes. An experienced CDMO will be equipped and ready for high-throughput optimization of scalable fermentation processes, as well as GMP-compliant drug production and technology transfer, ensuring seamless scale-up to reach global consumers.

An example of CDMO excellence in the wake of a global pandemic

The advantages of CDMO partnerships became increasingly relevant—and better recognized—during the recent coronavirus pandemic. As COVID-19 cases rose, demand for vaccines and therapeutics skyrocketed, and an increasing number of biopharmaceutical companies looked to fast-track new drugs to market. Researchers at the California Institute of Technology (Caltech) and the University of Oxford were among many scientists that focused their attention on developing coronavirus-fighting technologies. They identified a potential biotherapeutic vaccine candidate: a "mosaic-8" nanoparticle that displays a SARS-CoV-2 spike protein receptor binding domain (RBD), as well as RBDs from seven other SARS-like betacoronaviruses.5 However, they required additional assistance to move this candidate from mammalian cells to a microbial production platform.6 

Seeking CDMO collaboration

A number of issues with the researchers’ initial attempts at vaccine production led to them outsourcing support for this project. For example, the initial method of vaccine biosynthesis that they developed—using multiple mammalian cell lines and Escherichia coli (E. coli) —was prohibitively costly and too complex to rapidly generate large quantities of product. In addition, the resulting nanoparticles were contaminated with endotoxins produced by the E. coli host, requiring extensive downstream purification steps. With limited time and funding available, the researchers required input from a CDMO to streamline, scale up, and reduce costs in the vaccine production process.

Benefits of external expertise

Partnering with an experienced CDMO in the biopharmaceutical space gave the researchers access to a wide variety of host organisms to produce the necessary RBDs and nanoparticles, including Pichia pastoris and Bacillus subtilis. Switching to these alternative microbial hosts improved the affordability, speed, scalability, and future adaptability of the novel vaccine.

. . . Around 44 percent of life science companies currently outsource most or all of their drug development processes.

The CDMO collaboration also benefited the next stage of this project: optimizing strain productivity and downstream processing. Having access to a variety of technologies enabled the researchers to achieve fast, accurate, and streamlined GMP-compliant purification of the vaccine components to low purity. Additionally, partnering with a multidisciplinary team gave the researchers access to a wide range of knowledge, so they could establish analytical methods to assess the distribution of RBDs on the nanoparticles, ensuring that they were displayed in an appropriate ratio to induce broad-spectrum immunity.

A next-generation coronavirus vaccine

With the help of an expert CDMO, the researchers enhanced and optimized each step in the vaccine production pathway and successfully developed an affordable, viable, and scalable manufacturing process for the future large-scale production of a broad-spectrum betacoronavirus vaccine. This project would not have been possible without the wide variety of host platforms, robust manufacturing capabilities, and broad scope of knowledge of the CDMO partner. 

Vaccine production is just one area where collaboration can have a positive impact; the influence of CDMO partnerships extends to a broad range of therapeutic ventures. Partnering with a CDMO gives companies a strategic advantage, enabling rapid, scalable, and low-cost drug development pathways that meet project specifications. These collaborations provide an opportunity for companies to turn their innovative ideas for new therapies into actual products, moving healthcare forward.

References

  1. Otto R, Santagostino A, Schrader U. Rapid growth in biopharma: Challenges and opportunities. McKinsey & Company. 2014. Accessed September 22, 2023. https://www.mckinsey.com/industries/life-sciences/our-insights/rapid-growth-in-biopharma.
  2. Kesik?Brodacka M. Progress in biopharmaceutical development. Biotechnology and Applied Biochemistry. 2017;65(3):306-322. doi:10.1002/bab.1617.
  3. Biopharmaceutical industry - Demand, Overview & Trends. Mordor Intelligence. 2023. Accessed September 22, 2023. https://www.mordorintelligence.com/industry-reports/global-biopharmaceuticals-market-industry
  4. Van Arnum P. CDMO outsourcing trends: cell and gene therapies. DCAT Value Chain Insights. 2022. Accessed September 22, 2023. https://www.dcatvci.org/features/cdmo-outsourcing-trends-cell-and-gene-therapies/.
  5. Cohen, A.A. et al. Mosaic RBD nanoparticles protect against challenge by diverse sarbecoviruses in animal models. Science. 2022;377(6606). doi:10.1126/science.abq0839.
  6. Ingenza collaboration with Caltech, Oxford University and CPI & secures $32M CEPI funding to advance next-generation coronavirus vaccine. Ingenza. 2022. Accessed September 22, 2023. https://www.ingenza.com/ingenza-collaboration-with-caltech-oxford-university-and-cpi-secures-32m-cepi-funding-to-advance-next-generation-coronavirus-vaccine/.